The Neurological Research Center (Epilepsy) at Yale is organized as a widely based investigative effort into mechanisms of epileptic seizures and their control, and of biological phenomena associated with seizures, with the aim of discerning factors responsible for the occurrence, frequency and nature of seizure disorders, and how they can be controlled. Both experimental and clinical studies are oriented towards the development of physiological, biochemical-metabolic and pharmacologic methods effective for treatment and control of epileptic seizures. The research includes investigations of physiological, biochemical and structural correlates of cerebral excitability changes and mechanisms related to antiepileptic drug action. The component projects in this research program are: basic cellular neurophysiological mechanisms of antiepileptic drug actions (utilizing invertebrate neurons); patho-physiology of mammalian neocortical epilepsy (role of laminar susceptibility and interaction); role of calcium and calmodulin-stimulated protein phosphorylation in seizure states; calcium, transmitter release and antiepileptic drug action; nuclear magnetic resonance metabolic studies (carbon and phosphorus related) of biochemical changes in "kindled" brain; epilepsy, taniepileptic drugs and sex hormones (menstrual cycle and epilepsy in female, and testosterone changes in males); evaluation of depth electroencephalagraphy in criteria for surgical treatment of focal epilepsy, comparison with metabolic "imaging".